Nygaard / Sinclair / Lett Effects of Low Dose and Low Dose Rate Radiation

1. Auflage 2013
ISBN: 978-1-4832-8183-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 348 Seiten

Advances in Radiation Biology, Volume 6: Effects of Low Dose and Low Dose Rate Radiation examines the biological effects of low dose and low dose rate ionizing radiation on a broad scale, covering various articles from microdosimetry to analyses of human responses. Estimates of the effects on humans from low doses or from sustained exposures to low dose rates of ionizing radiations are of critical importance for the assessment of radiation risks under occupational and environmental conditions. This book consists of such knowledge that is essential for radiation protection and governmental regulatory activities pertaining to radiation exposure. This volume is intended for radiobiologists, radiation epidemiologists, radiation physicists, radiation safety personnel, health officials, and individuals involved in regulatory activities.

Autoren/Hrsg.

Nygaard, Oddvar F.

Sinclair, Warren K.

Lett, John T.

Inhaltsverzeichnis

1;Front Cover;1
2;Advances in Radiation Biology: Effects of Low Dose and Low Dose Rate Radiation;4
3;Copyright Page ;5
4;Table of Contents;6
5;Preface;12
6;Chapter 1. Introduction and Overview;14
6.1;References;19
7;Chapter 2. Track Structure Considerations in Low Dose and Low Dose Rate Effects of Ionizing Radiation;20
7.1;I. Introduction;20
7.2;II. Features of Radiation Tracks;22
7.3;III. Dose Responses and Extrapolation to Low Doses;33
7.4;IV. Conclusions;52
7.5;References;54
8;Chapter 3. Dose–Time–Response Models for Radiation Carcinogenesis;58
8.1;I. Introduction;58
8.2;II. Descriptive Models;59
8.3;III. Radiobiological Principles;74
8.4;IV. Mechanistic Models;77
8.5;V. Directions of Future Research;85
8.6;VI. Conclusions;87
8.7;References;88
9;Chapter 4. Radiation-Induced Mutation in Mammalian Cells at Low Doses and Dose Rates;90
9.1;I. Introduction;90
9.2;II. Mutation Measurements;94
9.3;III. Comment on Mutation Data;106
9.4;IV. Novel Mutation Systems: Enhancing Mutant Detection;116
9.5;V. The Bottom Line(s);122
9.6;Appendix 1: Mammalian Cell Line Sensitivities;123
9.7;Appendix 2: A Brief Survey of the Nature of Radiation-Induced Mutations;124
9.8;References;130
10;Chapter 5. Commentary to Thacker: A Consideration of the Mechanisms of Induction of Mutations in Mammalian Cells by Low Doses and Dose Rates of Ionizing Radiation;138
10.1;I. Introduction;138
10.2;II. DNA Damage, Repair, and Mutations;139
10.3;III. Mechanism of Induction of Chromosomal Mutations by Ionizing Radiations;140
10.4;IV. Mutation Induction (Chromosomal and Point) by Ionizing Radiation;145
10.5;V. Conclusion;146
10.6;References;147
11;Chapter 6. Oncogenic Cell Transformation in Vitro;150
11.1;I. Introduction;150
11.2;II. Cellular and Molecular Events in Oncogenic Transformation;151
11.3;III. Choice of Cellular Systems: Criteria and Endpoints for Oncogenic Transformation;160
11.4;IV. In Vivo Correlations of Transformation in Vitro;165
11.5;V. Concluding Remarks: Future Research Directions;166
11.6;References;168
12;Chapter 7. Commentary 1 to Cox and Little: The Unbridged Gap between in Vivo and in Vitro Models for Evaluation of Low Dose, Low Dose Rate Radiation-Induced Oncogenic Transformation;172
12.1;I. Introduction;172
12.2;II. Stages of Neoplastic Development;174
12.3;III. Model Systems for Studying Neoplastic Progression;176
12.4;IV. Summary;177
12.5;Acknowledgments;178
12.6;References;178
13;Chapter 8. Commentary 2 to Cox and Little: Radiation-Induced Oncogenic Transformation: The Interplay between Dose, Dose Protraction, and Radiation Quality;180
13.1;I. Introduction;180
13.2;II. Review of Pertinent Experimental Data;182
13.3;III. Biophysical Modeling of Inverse Dose Rate Effects;183
13.4;IV. Practical Consequences in the Field of Radiation Protection;186
13.5;V. Conclusions;190
13.6;Acknowledgments;190
13.7;References;190
14;Chapter 9. The Role of Animal Experiments in Estimates of Radiation Risk;194
14.1;I. Introduction;194
14.2;II. Stochastic Effects;197
14.3;III. The Use of Experimental Data: Qualitative and Quantitative;202
14.4;IV. Protracted and Low Dose Rate Studies;205
14.5;V. Transfer to Risk Estimates across Populations;206
14.6;VI. Summary;208
14.7;Acknowledgments;209
14.8;References;209
15;Chapter 10. Commentary to Fry: Radiation Carcinogenesis Studies in Animals—Advantages, Limitations, and Caveats;212
15.1;I. Introduction;212
15.2;II. Random Processes and Carcinogenic Effects;213
15.3;III. Molecular Biology of Radiation Carcinogenesis;215
15.4;IV. The Grade of Malignancy and the Absorbed Dose;217
15.5;V. The Relative Biological Effectiveness of High Linear Energy Transfer Radiation;219
15.6;VI. Influence of the Time Factor for High Linear Energy Transfer Radiation;220
15.7;VII. Caveats of Cancer Risks for Humans;223
15.8;References;225
16;Chapter 11. Radiation Carcinogenesis in Humans;228
16.1;I. Introduction;228
16.2;II. Carcinogenesis;229
16.3;III. Conclusions;267
16.4;References;267
17;Chapter 12. Commentary 1 to Schull and Weiss: Low Dose Extrapolation, Time following Exposure, and Transport between Populations;272
17.1;I. Low Dose Extrapolation;273
17.2;II. Changes in Excess Risk over Time following Exposure;279
17.3;III. Transport of Risk Estimates from One Population to Another;282
17.4;References;284
18;Chapter 13. Commentary 2 to Schull and Weiss: Human Cellular Radiosensitivity— The Search for the Diagnostic Holy Grail or a Poisoned Chalice;286
18.1;I. Introduction;286
18.2;II. The Response of Individuals;288
18.3;III. Measurements of Cellular Radiosensitivity;289
18.4;IV. Genetically Disposed Individuals;293
18.5;V. Modifications to Survival Assays;294
18.6;VI. Sensitivity of Tumor-Derived Cells;297
18.7;VII. Other Assays;298
18.8;VIII. Conclusions and the Future;300
18.9;Acknowledgments;301
18.10;References;301
19;Chapter 14. Commentary 3 to Schull and Weiss: Increased Definition of Abnormal Radiosensitivity Using Low Dose Rate Testing;306
19.1;I. Introduction;306
19.2;II. Evidence for DNA Repair Involvement in Cases of Protection at Low Dose Rates;307
19.3;III. Chronic Exposure Expands the Range of Radioresponse;309
19.4;IV. Increased Resolution of Mildly Hypersensitive Responses Is Possible with Chronic Dose Delivery;312
19.5;V. Possible Mechanisms of Protection on Dose Rate Protraction;313
19.6;Acknowledgments;314
19.7;References;314
20;Chapter 15. Radiation Protection: Recent Recommendations of the ICRP and the NCRP and Their Biological Basis;316
20.1;I. Introduction;316
20.2;II. History of ICRP and NCRP Recommendations;317
20.3;III. Deterministic Effects, Stochastic Effects, and Detriment;318
20.4;IV. The Risk of Radiation-Induced Cancer to 1985;321
20.5;V. Recent Evaluations of the Risk of Radiation-Induced Fatal Cancer;323
20.6;VI. Uncertainties in Risk Coefficients for Fatal Cancer;327
20.7;VII. Tissue Weighting Factors (wT)and Detriment;328
20.8;VIII. Radiations Other Than Low Linear Energy Transfer X and . rays;330
20.9;References;335
21;Index;338

Leseproben

Introduction and Overview

Oddvar F. Nygaard* and Warren K. Sinclair†,     *Department of Radiology, Division of Radiation Biology, Case Western Reserve University, Cleveland, Ohio 44106; †National Council on Radiation Protection and Measurements Bethesda, Maryland 20814

Estimates of the effects on humans from low doses or from sustained exposures to low dose rates of ionizing radiations are of critical importance for the assessment of radiation risks under occupational and environmental conditions. Such knowledge is essential for radiation protection and for governmental regulatory activities pertaining to radiation exposure.

The effects or end points relevant to our concerns about low dose/low dose rate exposures are stochastic in nature and include both cancers and mutations in the exposed individuals, the latter manifested in the offspring. Stochastic effects are believed to have the same severity at all doses but with the frequency of the effect being a function of the dose. Compared to our knowledge about most other potentially harmful environmental and occupational exposures, we have a great deal of quantitative knowledge about the effects of radiation; however, this knowledge is limited in several respects. Most observations have been obtained as the result of large doses (acute or cumulative) and often at relatively high dose rates. The human epidemiological data are quite limited, making it important to draw on data from animal experiments and investigations of cell systems to gain an understanding of the underlying mechanisms. Such understanding will aid in developing models that will support the extrapolation of results from the high dose data to the low dose and low dose rate regions.

Over the years, a number of publications have addressed these problems in various ways [National Academy of Sciences/National Research Council (NAS/NRC), 1980, 1988, 1990; United Nations Scientific Commit tee on the Effects of Atomic Radiation (UNSCEAR), 1977, 1982, 1986, 1988; National Institutes of Health (NIH), 1985; Woodhead 1985; Russell 1987; Baverstock and Stather, 1989]. Recently, a feasibility study of considerable relevance to the subject of this volume, entitled was published under the aegis of the United States Nuclear Energy Commission (NRC, 1990). These publications were either the reports of specific panels convened to review and assess the available data or the proceedings of symposia organized for the purpose of presenting new information and insight.

Radiation protection bodies consisting of professional scientists, such as the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP) in the United States, have also played a major role in the further assessment of the radiobiological and radioepidemiological information, especially for radiation protection purposes.

To generate the present volume a relatively small group of scientists was asked to address a number of issues, the understanding of which was felt to be necessary for projecting the effects on humans of low doses and/or low dose rates of ionizing radiations. The treatment of each subject or issue was not necessarily to be an exhaustive review, although the approaches of the authors differ greatly in this regard; rather, the issues were to be identified, including gaps in our present understanding, and suggestions provided as to research that might bring us closer to the needed answers. In addition to the seven main articles (those by D. T. Goodhead, S. B. Curtis and D. C. Thomas, J. Thacker, R. Cox and J. B. Little, R. J. M. Fry, W. J. Schull and K. M. Weiss, and W. K. Sinclair) a number of additional investigators were asked to provide commentaries in specific areas related to these articles. These commentaries (or counterpoints) do not constitute critiques but rather expand on specific points or address specific issues that had not been dealt with directly in the main articles. In addition, the authors of the commentaries were encouraged not to shy away from speculation or from controversial ideas. The interspersing of these commentaries is meant to provide a more penetrating treatment of certain issues and to make the volume overall more interesting and informative.

Our understanding and interpretation of the biological effects of ionizing radiations must be consistent with what we know to occur at the physical and biophysical level. This is especially important in the case of low doses and low dose rates, where microdosimetric principles become especially significant. In the second article, , D. T. Goodhead provides the physical foundations for much of the later material in this volume.

As already mentioned, the development of models that will describe the biological response to radiation for a given end point (in the present case, primarily the induction of malignancies) is especially important for the extrapolation from observations made after relatively high doses to the realm of low doses and low dose rates. Such models are developed along two different lines: models that aim to describe the observed data mathematically, as simply and with as much fidelity as possible, but without necessarily subscribing to an underlying biological model, and models, for which presumed biological mechanisms provide the primary driving forces. Both types of models are important in our attempts to predict and project the effects of radiation over the entire dose range of interest as well as into the future. Eventually, the two types of models will have to merge as our biological knowledge increases. An examination of by S. B. Curtis and D. C. Thomas is the third article presented.

It is generally assumed that a mutational event is involved as the first or initiation step of carcinogenesis. Genetic mutations are also an important element in our consideration of radiation protection and the formulation of protection standards because of the contribution to the overall health detriment from exposure. The subject of mutagenesis resulting from exposure to ionizing radiation is covered extensively by J. Thacker in the fourth article, This chapter addresses mutation systems, mutation measurements in mammalian somatic and germ cells and in other organisms, issues relating to dose rates and low doses in mutation systems, novel mutation systems enhancing mutant detection, and the “bottom line” in radiation mutagenesis today.

An associated commentary entitled , by R. Julian Preston, represents an attempt to develop a general model for mutation induction that might be valid for both low- and high-linear energy transfer (LET) radiations and compares its predictions to available experimental data.

Malignant transformation of rodent cells has for many years served as a model system for oncogenic transformation , with the advantages of allowing the controlled study of factors that are involved in, and can modulate, the process. In this way the transformation model is an important tool in the elucidation of the mechanism of carcinogenesis. In the sixth article, R. Cox and J. B. Little review in Vitro. The authors deal with many of the technical difficulties and limitations of these studies as well as point the way to future research in this field. A related commentary by M. Terzaghi-Howe is entitled This commentary deals especially with the potential merits of the combination of culture systems with models (such as the author’s own tracheal mucosa system) for the study of neoplastic progression.

A second commentary associated with the article by R. Cox and J. B. Little is entitled , by D. J. Brenner and E. J. Hall. It considers the so-called “inverse dose rate effect” observed in the case of malignant transformation as well as with high-LET radiation. In this commentary the authors summarize the diverse results obtained in this area, which appear to follow a pattern with respect to dose, dose rate and LET, and also describe a model that assumes an increased sensitivity to transformation in a small fraction of the cell cycle. The proposed model enables predictions to be made for the maximum potential ratio of effects of protracted vs single doses of neutrons and protons.

is the subject of the ninth article, by R. J. M....